EP 2119717 A1 20091118 - 8-[3-amino-piperidin-1-yl]-xanthins, their production and utilisation as DPP IV inhibitors
Title (en)
8-[3-amino-piperidin-1-yl]-xanthins, their production and utilisation as DPP IV inhibitors
Title (de)
8-[3-amino-piperidin-1-yl]-Xanthine, deren Herstellung und deren Verwendung als DPP IV Hemmer
Title (fr)
8-[3-amino-pipéridine-1-yl]-xanthine, leur fabrication et leur utilisation en tant que complexe DDP IV
Publication
Application
Previously filed application
05707354 20050212 EP
Priority
- EP 05707354 A 20050212
- DE 102004008112 A 20040218
- DE 102004012921 A 20040317
- DE 102004032263 A 20040703
Abstract (en)
7-Butynyl-8-(3-amino-1-piperidinyl)xanthine derivatives (I) are new. 7-Butynyl-8-(3-amino-1-piperidinyl)xanthine derivatives of formula (I) and their tautomers, isomers and salts are new. R : benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,6-difluoro-benzyl, 3,4-difluoro-benzyl, 2-chlorobenzyl, 3-chlorobenzyl or 4-chlorobenzyl, 2-trifluoromethyl-benzyl, 3-trifluoromethyl-benzyl or 4-trifluoromethyl-benzyl, 3-trifluoromethoxy-benzyl or 4-trifluoromethoxy-benzyl, 2-cyanobenzyl, 3-cyanobenzyl or 4-cyanobenzyl, 2,6-dicyanobenzyl, 3,4-dicyanobenzyl, 3,5-dicyanobenzyl, 2-trifluoromethyl-4-cyano-benzyl, 3-nitro-4-cyano-benzyl, 2-cyano-3-methoxy-benzyl, 2-cyano-4-methoxy-benzyl, 2-cyano-5-methoxy-benzyl, 2-cyano-4-fluoro-benzyl, 2-cyano-5-fluoro-benzyl, 2-cyano-6-fluoro-benzyl, 3-cyano-4-fluoro-benzyl, 4-cyano-3-fluorobenzyl, 2-fluoro-4-cyano-benzyl, 2-cyano-3-chlorobenzyl, 2-chloro-4-cyano-benzyl or 2-cyano-4-bromobenzyl, 2-methoxy-benzyl, 3-methoxy-benzyl, 4-methoxy-benzyl, 2-fluoro-3-methoxybenzyl, 2-fluoro-4-methoxy-benzyl, 2-fluoro-5-methoxy-benzyl, 3-fluoro-4-methoxybenzyl, 3,4-dimethoxy-benzyl, 3,5-dimethoxybenzyl or 3,4-dimethoxy-6-fluorobenzyl, (benzo[1,3]dioxol-5-yl)methyl, [(4-cyano-benzo[1,3]dioxol-5-yl)methyl, 2-(3-cyclopropyloxy-phenyl)-2-oxo-ethyl, 2-(3-cyclopropylmethoxy-phenyl)-2oxo-ethyl or 2-(3-cyclobutyloxy-phenyl)-2-oxo-ethyl, 2-oxo-2-[2-(pyridin-3-yl)-phenyl]-ethyl or 2-oxo-2-[2-(pyridin-4-yl)-phenyl]ethyl, (3-cyano-1-naphthyl)methyl, (1,4-dicyano-2-naphthyl)methyl or (2,4-dimethoxy-1-naphthyl)methyl, (furan-2-yl)methyl, (furan-3-yl)methyl, (5-bromo-furan-2-yl)methyl, (5-methylfuran-2-yl)methyl, (5-cyano-furan-2-yl)methyl or (5-methoxycarbonyl-furan-2yl)methyl, (pyridin-2-yl)methyl, (6-fluoro-pyridin-2-yl)methyl or (5-methoxy-pyridin-2-yl)methyl, (3-cyanopyridin-2-yl)methyl, (6-cyanopyridin-2- yl)methyl, (5-cyano-pyridin-2-yl)methyl, (4-cyano-pyridin-2-yl)methyl, (4-cyano-pyridin-3-yl)methyl, (3-cyanopyridin-4-yl)methyl, (2-cyano-pyridin-3-yl)methyl, (2-cyano-pyridin-4-yl)methyl, (5cyano-pyridin-3-yl)methyl, (6-cyano-pyridin-3-yl)methyl or (5-cyano-6-methoxypyridin-2-yl)methyl, (6-phenyl-pyridin-2-yl)methyl or ([2,2']bipyridinyl-6-yl)methyl, (pyrimidin-2-yl)methyl, (4-methyl-pyrimidin-2-yl)methyl or (4,6-dimethylpyrimidin-2-yl)methyl, (2-phenyl-pyrimidin-4-yl)methyl or (4-phenyl-pyrimidin-2-yl)methyl, [(1-methyl-1H-benzotriazol-5-yl)methyl], (6-fluoro-quinolin-2-yl)methyl, (7-fluoro-quinolin-2-yl)methyl, (2-methyl-quinolin-4-yl)methyl, (3-cyano-quinolin-2-yl)methyl, (3-cyano-4-methyl-quinolin-2-yl)methyl, (4-cyano-quinolin-2-yl)methyl, (5-cyano-quinolin-2-yl)methyl, (6-cyano-quinolin-2-yl)methyl, (6-amino-quinolin-2-yl)methyl, (8-amino-quinolin-2-y1)methyl, (4-methoxy-quinolin-2-yl)methyl, (6-methoxy-quinolin-2-yl)methyl, (6,7-dimethoxyquinolin-2-yl)methyl or (8-cyano-quinolin-7-yl)methyl, (1-cyano-isoquinolin-3-yl)methyl, (4-cyano-isoquinolin-1-yl)methyl, (4-cyanoisoquinolin-3-yl)methyl or [(4-(pyridin-2-yl)-isoquinolin-1-yl)methyl, (quinazolin-6-yl)methyl, (quinazolin-7-yl)methyl, (2-methyl-quinazolin-4yl)methyl, (4,5-dimethyl-quinazolin-2-yl)methyl, (4-ethyl-quinazolin-2-yl)methyl, (4-cyclopropyl-quinazolin-2-yl)methyl, (2-phenyl-quinazolin-4-yl)methyl, (4-cyanoquinazolin-2-yl)methyl, (4-phenylamino-quinazolin-2-yl)methyl or (4-benzylaminoquinazolin-2-yl)methyl, (quinoxalin-5-yl)methyl, (quinoxalin-6-yl)methyl or (2,3-dimethyl-quinoxalin-6-yl)methyl, or ([1,5]naphthyridin-3-yl)methyl. An independent claim is also included for a process for preparing (I). [Image] ACTIVITY : Antidiabetic; Antiarthritic; Anorectic; Osteopathic; Tranquilizer; Hypotensive; Nephrotropic; Antiinflammatory; Antiulcer; Immunosuppressive; Virucide; Anti-HIV; Neuroprotective; Nootropic; Cytostatic; Cerebroprotective; Vasotropic; Antiparkinsonian; Antimigraine; Dermatological; Antipsoriatic; Antidepressant; Neuroleptic. MECHANISM OF ACTION : Dipeptidyl peptidase IV (DPP IV) inhibitor. 1-(4-Benzylamino-4-quinazolinylmethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-1-piperidinyl)xanthine had an IC50 of 6 nM against DPP IV activity in Caco-2 cell extracts.
Abstract (de)
Die vorliegende Erfindung betrifft substituierte Xanthine der allgemeinen Formel in der R wie in Anspruch 1 definiert sind, deren Tautomere, deren Stereoisomere, deren Gemische und deren Salze, welche wertvolle pharmakologische Eigenschaften aufweisen, insbesondere eine Hemmwirkung auf die Aktivität des Enzyms Dipeptidylpeptidase-IV (DPP-IV).
IPC 8 full level
C07D 473/04 (2006.01); A61K 31/437 (2006.01); A61P 3/10 (2006.01)
CPC (source: EP KR)
A61K 31/44 (2013.01 - KR); A61P 1/02 (2017.12 - EP); A61P 1/04 (2017.12 - EP); A61P 1/18 (2017.12 - EP); A61P 3/00 (2017.12 - EP); A61P 3/04 (2017.12 - EP); A61P 3/10 (2017.12 - EP); A61P 5/00 (2017.12 - EP); A61P 5/02 (2017.12 - EP); A61P 7/10 (2017.12 - EP); A61P 9/10 (2017.12 - EP); A61P 9/12 (2017.12 - EP); A61P 13/08 (2017.12 - EP); A61P 13/12 (2017.12 - EP); A61P 15/08 (2017.12 - EP); A61P 15/16 (2017.12 - EP); A61P 17/00 (2017.12 - EP); A61P 17/06 (2017.12 - EP); A61P 19/02 (2017.12 - EP); A61P 19/10 (2017.12 - EP); A61P 25/00 (2017.12 - EP); A61P 25/06 (2017.12 - EP); A61P 25/16 (2017.12 - EP); A61P 25/24 (2017.12 - EP); A61P 25/28 (2017.12 - EP); A61P 29/00 (2017.12 - EP); A61P 31/12 (2017.12 - EP); A61P 31/18 (2017.12 - EP); A61P 35/00 (2017.12 - EP); A61P 35/02 (2017.12 - EP); A61P 35/04 (2017.12 - EP); A61P 37/06 (2017.12 - EP); A61P 43/00 (2017.12 - EP); C07D 473/04 (2013.01 - EP KR); C07D 473/06 (2013.01 - KR)
Citation (applicant)
- WO 02068420 A1 20020906 - BOEHRINGER INGELHEIM PHARMA [DE], et al
- WO 0202560 A2 20020110 - NOVO NORDISK AS [DK], et al
- WO 03004496 A1 20030116 - NOVO NORDISK AS [DK]
- WO 03024965 A2 20030327 - NOVO NORDISK AS [DK], et al
- WO 2004018468 A2 20040304 - BOEHRINGER INGELHEIM PHARMA [DE], et al
- WO 2004048379 A1 20040610 - SUMITOMO PHARMA [JP], et al
- JP 2003300977 A 20031021 - SUMITOMO PHARMA
- EP 1338595 A2 20030827 - EISAI CO LTD [JP]
- ALLINGER N. L; ELIEL E. L: "Topics in Stereochemistry", vol. 6, 1971, WILEY INTERSCIENCE
- REIHER ET AL.: "Increased expression of intestinal cell line Caco-2", PROC. NATL. ACAD. SCI., vol. 90, 1993, pages 5757 - 5761
Citation (search report)
- [DX] WO 02068420 A1 20020906 - BOEHRINGER INGELHEIM PHARMA [DE], et al
- [XDP] WO 2004018468 A2 20040304 - BOEHRINGER INGELHEIM PHARMA [DE], et al
Designated contracting state (EPC)
AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR
DOCDB simple family (publication)
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DOCDB simple family (application)
EP 2005001427 W 20050212; AR P050100578 A 20050218; AT 05707354 T 20050212; AU 2005219508 A 20050212; BR PI0507873 A 20050212; CA 2555050 A 20050212; CN 201110084216 A 20050212; CY 091100791 T 20090723; DE 502005007196 T 20050212; DK 05707354 T 20050212; EA 200601496 A 20050212; EA 200801601 A 20050212; EC SP066775 A 20060818; EP 05707354 A 20050212; EP 09158875 A 20050212; ES 05707354 T 20050212; HK 07111729 A 20071031; HR P20090346 T 20090615; IL 17692006 A 20060718; IL 21726811 A 20111229; JP 2006553504 A 20050212; JP 2010178510 A 20100809; KR 20067019124 A 20060918; ME P23509 A 20050212; MY PI20050575 A 20050216; NO 20062688 A 20060609; NZ 54890105 A 20050212; PE 2005000183 A 20050216; PL 05707354 T 20050212; PT 05707354 T 20050212; RS P20090303 A 20050212; SI 200530736 T 20050212; TW 94104568 A 20050217; UY 28749 A 20050215